Opportunistic salpingectomy between 2011 and 2016: a descriptive analysis.

BACKGROUND: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during hysterectomy for benign indications or instead of tubal ligation, for the purpose of preventing ovarian cancer. We determined rates of OS at the time of hysterectomy and tubal sterilization and examined how they changed over the study period. METHODS: Using data from the Canadian Institute for Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories (except Quebec) between the fiscal years 2011 and 2016, we conducted a descriptive analysis of all patients aged 15 years or older who underwent hysterectomy or tubal sterilization. We excluded those with diagnostic codes for any gynecologic cancer and those who underwent unilateral salpingectomy. We examined the proportion who had OS during their hysterectomy and compared the proportion of tubal sterilizations that were OS with the proportion that were tubal ligations. RESULTS: A total of 318 528 participants were included in the study (mean age 42.5 yr). The proportion of hysterectomies that included OS increased from 15.4% in 2011 to 35.5% by 2016. With respect to tubal sterilization, the rate of OS increased from 6.5% of all tubal sterilizations in 2011 to 22.0% in 2016. There was considerable variation across jurisdictions in 2016, with British Columbia having the highest rates (53.2% of all hysterectomies and 74.0% of tubal sterilizations involved OS). INTERPRETATION: The rates of OS increased between 2011 and 2016, but there was considerable variation across the included jurisdictions. Our study indicates room for rates of OS to increase across many of the included jurisdictions.

Breast Density and Risk of Interval Cancers: The Effect of Annual Versus Biennial Screening Mammography Policies in Canada.

Regular screening mammography reduces breast cancer mortality. However, in women with dense breasts, the performance of screening mammography is reduced, which is reflected in higher interval cancer rates (ICR). In Canada, population-based screening mammography programs generally screen women biennially; however, some provinces and territories offer annual mammography for women with dense breast tissue routinely and/or on recommendation of the radiologist. This study compared the ICRs in those breast screening programs with a policy of annual vs. those with biennial screening for women with dense breasts. Among 148,575 women with dense breasts screened between 2008 to 2010, there were 288 invasive interval breast cancers; screening programs with policies offering annual screening for women with dense breasts had fewer interval cancers 63/70,814 (ICR 0.89/1000, 95% CI: 0.67-1.11) compared with those with policies of usual biennial screening 225/77,761 (ICR 1.45 /1000 (annualized), 95% CI: 1.19-1.72) i.e. 63% higher (p = 0.0016). In screening programs where radiologists' screening recommendations were able to be analyzed, a total of 76,103 women were screened, with 87 interval cancers; the ICR was lower for recommended annual (65/69,650, ICR 0.93/1000, 95% CI: 0.71, 1.16) versus recommended biennial screening (22/6,453, ICR 1.70/1000 (annualized), 95%CI: 0.70, 2.71)(p = 0.0605). Screening program policies of annual as compared with biennial screening in women with dense breasts had the greatest impact on reducing interval cancer rates. We review our results in the context of current dense breast notification in Canada.

Population-Based Cancer Survival in Canada and the United States by Socioeconomic Status: Findings from the CONCORD-2 Study.

Background: Population-based cancer survival provides insight into the effectiveness of health systems to care for all residents with cancer, including those in marginalized groups. Methods: Using CONCORD-2 data, we estimated 5-year net survival among patients diagnosed 2004-2009 with one of 10 common cancers, and children diagnosed with acute lymphoblastic leukemia (ALL), by socioeconomic status (SES) quintile, age (0-14, 15-64, ≥65 years), and country (Canada or United States). Results: In the lowest SES quintile, survival was higher among younger Canadian adults diagnosed with liver (23% vs 15%) and cervical (78% vs 68%) cancers and with leukemia (62% vs 56%), including children diagnosed with ALL (92% vs 86%); and higher among older Americans diagnosed with colon (62% vs 56%), female breast (87% vs 80%), and prostate (97% vs 85%) cancers. In the highest SES quintile, survival was higher among younger Americans diagnosed with stomach cancer (33% vs 27%) and younger Canadians diagnosed with liver cancer (31% vs 23%); and higher among older Americans diagnosed with stomach (27% vs 22%) and prostate (99% vs 92%) cancers. Conclusions: Among younger Canadian cancer patients in the lowest SES group, greater access to health care may have resulted in higher cancer survival, while higher screening prevalence and access to health insurance (Medicare) among older Americans during the period of this study may have resulted in higher survival for some screen-detected cancers. Higher survival in the highest SES group for stomach and liver may relate to treatment differences. Survival differences by age and SES between Canada and the United States may help inform cancer control strategies.

Transforming Canada's role in global cancer control.

Cancer has not been an explicit priority of Canada's international health and development agenda, but it is key to realising the country's Sustainable Development Goal commitments. Multiple converging political, health, and social forces could now drive support for a more integrated Canadian approach to global cancer control. Success will depend on the extent to which Canadian leaders and institutions can build consensus as a community and agree to work together. Collaboration should include agreement on the framing and prioritisation of the core issues, building a broad coalition base, aligning with priorities of international partners, and on a governance structure that reflects the principles of equity, diversity, and inclusion. This Series paper will discuss global cancer control within Canada's global health agenda, how Canada can address its history of colonisation and present-day disparities in its global work, and the challenges and opportunities of creating a Canadian global cancer control network.

The osmorespiratory compromise: physiological responses and tolerance to hypoxia are affected by salinity acclimation in the euryhaline Atlantic killifish (Fundulus heteroclitus).

The characteristics of the fish gill that maximize gas exchange are the same that promote diffusion of ions and water to and from the environment; therefore, physiological trade-offs are likely to occur. Here, we investigated how salinity acclimation affects whole-animal respiratory gas exchange during hypoxia using Fundulus heteroclitus, a fish that inhabits salt marshes where salinity and oxygen levels vary greatly. Salinity had marked effects on hypoxia tolerance, with fish acclimated to 11 and 35 ppt showing much longer time to loss of equilibrium (LOE) in hypoxia than 0 ppt-acclimated fish. Fish acclimated to 11 ppt (isosmotic salinity) exhibited the greatest capacity to regulate oxygen consumption rate (MO2 ) under hypoxia, as measured through the regulation index (RI) and Pcrit At 35 ppt, fish had a higher routine metabolic rate (RMR) but a lower RI than fish at 11 ppt, but there were no differences in gill morphology, ventilation or blood O2 transport properties between these groups. In contrast, 0 ppt-acclimated fish had the highest ventilation and lowest O2 extraction efficiency in normoxia and hypoxia, indicating a higher ventilatory workload in order to maintain similar levels of MO2 These differences were related to alterations in gill morphology, where 0 ppt-acclimated fish had the smallest lamellar surface area with the greatest epithelial cell coverage (i.e. thicker lamellae, longer diffusion distance) and a larger interlamellar cell mass, contrasting with 11 ppt-acclimated fish, which had overall the highest respiratory surface area. The alteration of an array of physiological parameters provides evidence for a compromise between salinity and hypoxia tolerance in killifish acclimated to freshwater.

Progress in cancer survival, mortality, and incidence in seven high-income countries 1995-2014 (ICBP SURVMARK-2): a population-based study.

BACKGROUND: Population-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends. METHODS: In this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control. FINDINGS: In 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995-2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010-14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer. INTERPRETATION: The joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Mitochondrial Ecophysiology: Assessing the Evolutionary Forces That Shape Mitochondrial Variation.

The mitonuclear species concept hypothesizes that incompatibilities between interacting gene products of the nuclear and mitochondrial genomes are a major factor establishing and maintaining species boundaries. However, most of the data available to test this concept come from studies of genetic variation in mitochondrial DNA, and clines in the mitochondrial genome across contact zones can be produced by a variety of forces. Here, we show that using a combination of population genomic analyses of the nuclear and mitochondrial genomes and studies of mitochondrial function can provide insight into the relative roles of neutral processes, adaptive evolution, and mitonuclear incompatibility in establishing and maintaining mitochondrial clines, using Atlantic killifish (Fundulus heteroclitus) as a case study. There is strong evidence for a role of secondary contact following the last glaciation in shaping a steep mitochondrial cline across a contact zone between northern and southern subspecies of killifish, but there is also evidence for a role of adaptive evolution in driving differentiation between the subspecies in a variety of traits from the level of the whole organism to the level of mitochondrial function. In addition, studies are beginning to address the potential for mitonuclear incompatibilities in admixed populations. However, population genomic studies have failed to detect evidence for a strong and pervasive influence of mitonuclear incompatibilities, and we suggest that polygenic selection may be responsible for the complex patterns observed. This case study demonstrates that multiple forces can act together in shaping mitochondrial clines, and illustrates the challenge of disentangling their relative roles.

Subspecies differences in thermal acclimation of mitochondrial function and the role of uncoupling proteins in killifish.

Thermal effects on mitochondrial efficiency and ATP production can influence whole-animal thermal tolerance and performance. Thus, organisms may have the capacity to alter mitochondrial processes through acclimation or adaptation to mitigate these effects. One possible mechanism is through the action of uncoupling proteins (UCPs), which can decrease the proton-motive force independent of the production of ATP. To test this hypothesis, we examined the mRNA expression patterns of UCP isoforms and characterized the effects of thermal acclimation and putative local thermal adaptation on mitochondrial capacity, proton leak and P/O ratios in two subspecies of Atlantic killifish (Fundulus heteroclitus). Ucp1 was the dominant isoform in liver and was more highly expressed in northern killifish. We found that cold acclimation increased mitochondrial capacity (state III and maximum substrate oxidation capacity), state II membrane potential, proton leak and P/O ratios in northern, but not southern, killifish liver mitochondria. Palmitate-induced mitochondrial uncoupling was detected in northern, but not southern, killifish liver mitochondria, consistent with the differences in Ucp mRNA expression between the subspecies. Taken together, our data suggest that mitochondrial function is more plastic in response to thermal acclimation in northern killifish than in southern killifish and that UCP1 may play a role in regulating the proton-motive force in northern, but not southern, killifish in response to thermal acclimation. These data demonstrate the potential for adaptive variation in mitochondrial plasticity in response to cold.

Integrative Population and Physiological Genomics Reveals Mechanisms of Adaptation in Killifish.

Adaptive divergence between marine and freshwater (FW) environments is important in generating phyletic diversity within fishes, but the genetic basis of this process remains poorly understood. Genome selection scans can identify adaptive loci, but incomplete knowledge of genotype-phenotype connections makes interpreting their significance difficult. In contrast, association mapping (genome-wide association mapping [GWAS], random forest [RF] analyses) links genotype to phenotype, but offer limited insight into the evolutionary forces shaping variation. Here, we combined GWAS, RF, and selection scans to identify loci important in adaptation to FW environments. We utilized FW-native and brackish water (BW)-native populations of Atlantic killifish (Fundulus heteroclitus) as well as a naturally admixed population between the two. We measured morphology and multiple physiological traits that differ between populations and may contribute to osmotic adaptation (salinity tolerance, hypoxia tolerance, metabolic rate, body shape) and used a reduced representation approach for genome-wide genotyping. Our results show patterns of population divergence in physiological capabilities that are consistent with local adaptation. Population genomic scans between BW-native and FW-native populations identified genomic regions evolving by natural selection, whereas association mapping revealed loci that contribute to variation for each trait. There was substantial overlap in the genomic regions putatively under selection and loci associated with phenotypic traits, particularly for salinity tolerance, suggesting that these regions and genes are important for adaptive divergence between BW and FW environments. Together, these data provide insight into the mechanisms that enable diversification of fishes across osmotic boundaries.

Thermal acclimation and subspecies-specific effects on heart and brain mitochondrial performance in a eurythermal teleost (Fundulus heteroclitus).

Mitochondrial performance may play a role in setting whole-animal thermal tolerance limits and their plasticity, but the relative roles of adjustments in mitochondrial performance across different highly aerobic tissues remain poorly understood. We compared heart and brain mitochondrial responses to acute thermal challenges and to thermal acclimation using high-resolution respirometry in two locally adapted subspecies of Atlantic killifish (Fundulus heteroclitus). We predicted that 5°C acclimation would result in compensatory increases in mitochondrial performance, while 33°C acclimation would cause suppression of mitochondrial function to minimize the effects of high temperature on mitochondrial metabolism. In contrast, acclimation to both 33 and 5°C decreased mitochondrial performance compared with fish acclimated to 15°C. These adjustments could represent an energetic cost-saving mechanism at temperature extremes. Acclimation responses were similar in both heart and brain; however, this effect was smaller in the heart, which might indicate its importance in maintaining whole-animal thermal performance. Alternatively, larger acclimation effects in the brain might indicate greater thermal sensitivity compared with the heart. We detected only modest differences between subspecies that were dependent on the tissue assayed. These data demonstrate extensive plasticity in mitochondrial performance following thermal acclimation in killifish, and indicate that the extent of these responses differs between tissues, highlighting the importance and complexity of mitochondrial regulation in thermal acclimation in eurytherms.

Mitochondrial genotype and phenotypic plasticity of gene expression in response to cold acclimation in killifish.

Adjustments of aerobic metabolic processes are critical components of organismal responses to environmental change that require tight coordination between the nuclear and mitochondrial genomes. Intraspecific differences in mitochondrial genotype can affect gene transcription in both genomes. Thus, variation in mitochondrial genotype may be associated with differences in the plasticity of gene expression when organisms are faced with changes in environmental conditions. Cold acclimation is known to result in metabolic responses involving increases in mitochondrial amount and capacity, suggesting that low temperatures may pose a particular challenge when coordinating the functions of the nuclear and mitochondrial genomes. In this study, we utilized RNA-seq to assess transcriptome-wide gene expression in the muscle of Atlantic killifish (Fundulus heteroclitus) from a population that contains segregating variation in mitochondrial genotype. We examined gene expression plasticity in response to 5 °C acclimation and the effects of mitochondrial genotype on this plasticity. Cold acclimation resulted in changes in gene expression consistent with up-regulation of genes involved in many cellular functions, including spliceosomal and proteasomal processes, and with down-regulation of genes involved in extracellular matrix, muscle contraction and oxidative phosphorylation functions. There were few differences in gene expression between killifish with different mitochondrial genotypes: 14 genes demonstrated significant interactions between mitochondrial genotype and acclimation temperature and three genes demonstrated effects of mitochondrial genotype alone. These results indicate that variation in mitochondrial genotype has modest effects on gene expression; the majority of which are revealed as differences in plasticity as a result of environmental change.

Rates of breast cancer surgery in Canada from 2007/08 to 2009/10: retrospective cohort study.

BACKGROUND: Surgery is a common and important component of breast cancer treatment. We assessed the rates of breast cancer surgery across Canada from 2007/08 to 2009/10. METHODS: We used hospital and day surgery data from the Canadian Institute for Health Information to assemble a cohort of women who had undergone breast cancer surgery. We identified the index surgical procedure and subsequent surgical procedures performed within 1 year for each woman included in the analysis. We calculated the crude mastectomy rate for each province, and we calculated the adjusted mastectomy rate for select jurisdictions using a logistic regression model fitted using age, neighbourhood income quintile and travel time. RESULTS: In total, 57 840 women underwent breast cancer surgery during the study period. Among women with unilateral invasive breast cancer, the crude mastectomy rate was 39%. Adjusted rates for mastectomy varied widely by province (26%-69%). The rate of re-excision within 1 year for women who had breast-conserving surgery as their index procedure was 23% and varied by province in terms of frequency and type (mastectomy or repeat breast-conserving surgery). Among women who underwent mastectomy for unilateral invasive breast cancer, 6% also underwent contralateral prophylactic mastectomy, and 7% had immediate breast reconstruction following surgery. Of mastectomy procedures, 20% were performed as day surgery; for breast-conserving surgery, 70% were performed as day surgery. INTERPRETATION: There is substantial interprovincial variation in surgical care for breast cancer in Canada. Further research is needed to better understand such variation, and continued monitoring should be the focus of quality initiatives.

Intrapersonal and social environment correlates of leisure-time physical activity for cancer prevention: a cross-sectional study among Canadian adults.

BACKGROUND: Little is known about the intrapersonal and social factors associated with sufficient physical activity (PA) for cancer prevention, which is greater than for cardiovascular health. METHODS: 1087 and 1684 randomly selected men and women, age 35-64, completed self-administered questionnaires on PA behavior and psycho-social characteristics. Using gender-stratified logistic regression, we investigated correlates of compliance with Canadian Society for Exercise Physiology PA guidelines for general health (150 min/wk), and the American Cancer Society (ACS; 225 min/wk) and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AIRC; 420 min/wk) guidelines for cancer prevention. RESULTS: Only 39% and 19% of men and women met ACS and WCRF/AICR guidelines, respectively. Self-efficacy, scheduling PA and friend social support were positively correlated with recommended PA for cancer prevention. In men, poor self-rated health and perceived negative outcomes were negatively correlated and hypertension was positively correlated with meeting cancer prevention guidelines. For women, not being married and having a companion for PA were positively correlated with meeting cancer prevention guidelines. CONCLUSIONS: Few adults participate in sufficient PA for cancer risk reduction. Multidimensional public health strategies that incorporate intrapersonal and social factors and are tailored for each gender are needed to promote PA for cancer prevention.

The Sedentary Time and Activity Reporting Questionnaire (STAR-Q): reliability and validity against doubly labeled water and 7-day activity diaries.

We determined measurement properties of the Sedentary Time and Activity Reporting Questionnaire (STAR-Q), which was designed to estimate past-month activity energy expenditure (AEE). STAR-Q validity and reliability were assessed in 102 adults in Alberta, Canada (2009-2011), who completed 14-day doubly labeled water (DLW) protocols, 7-day activity diaries on day 15, and the STAR-Q on day 14 and again at 3 and 6 months. Three-month reliability was substantial for total energy expenditure (TEE) and AEE (intraclass correlation coefficients of 0.84 and 0.73, respectively), while 6-month reliability was moderate. STAR-Q-derived TEE and AEE were moderately correlated with DLW estimates (Spearman's ρs of 0.53 and 0.40, respectively; P < 0.001), and on average, the STAR-Q overestimated TEE and AEE (median differences were 367 kcal/day and 293 kcal/day, respectively). Body mass index-, age-, sex-, and season-adjusted concordance correlation coefficients (CCCs) were 0.24 (95% confidence interval (CI): 0.07, 0.36) and 0.21 (95% CI: 0.11, 0.32) for STAR-Q-derived versus DLW-derived TEE and AEE, respectively. Agreement between the diaries and STAR-Q (metabolic equivalent-hours/day) was strongest for occupational sedentary time (adjusted CCC = 0.76, 95% CI: 0.64, 0.85) and overall strenuous activity (adjusted CCC = 0.64, 95% CI: 0.49, 0.76). The STAR-Q demonstrated substantial validity for estimating occupational sedentary time and strenuous activity and fair validity for ranking individuals by AEE.

Quality indicators for ductal carcinoma in situ (DCIS) of the breast: development using a multidisciplinary delphi process and its use in monitoring population-based treatment.

BACKGROUND AND OBJECTIVES: Evaluation of the management of DCIS poses challenges, as standard breast cancer outcome measures such as mortality do not apply. We have developed quality indicators (QIs) to measure the quality of DCIS treatment in Alberta, Canada. METHODS: A modified Delphi process was used to determine QIs in the treatment of DCIS after review of evidence-based clinical practice guidelines. Patients diagnosed with DCIS from 2000 to 2001 (cohort 1) and 2009-2010 (cohort 2) were identified from the Alberta Cancer Registry and QIs were retrospectively abstracted. RESULTS: The expert panel developed eight QIs to assess the overall quality of care for DCIS patients. Five hundred eighty eligible patients were identified in the two cohorts. There was significant improvement in radiation oncology referral, radiation post lumpectomy and complete pathology reporting. Axillary staging significantly increased from 20% (axillary dissection in cohort 1) to 60% (sentinel node biopsy in cohort 2). Other QIs did not differ significantly. CONCLUSIONS: By developing QIs, performance measures for DCIS may assessed and compared over time. Although there have been significant improvements with pathology reporting and radiation oncology assessment and treatment, axillary staging rates are unexpectedly high, necessitating further investigation.

The International Cancer Benchmarking Partnership: an international collaboration to inform cancer policy in Australia, Canada, Denmark, Norway, Sweden and the United Kingdom.

The International Cancer Benchmarking Partnership (ICBP) was initiated by the Department of Health in England to study international variation in cancer survival, and to inform policy to improve cancer survival. It is a research collaboration between twelve jurisdictions in six countries: Australia (New South Wales, Victoria), Canada (Alberta, British Columbia, Manitoba, Ontario), Denmark, Norway, Sweden, and the United Kingdom (England, Northern Ireland, Wales). Leadership is provided by policymakers, with academics, clinicians and cancer registries forming an international network to conduct the research. The project currently has five modules examining: (1) cancer survival, (2) population awareness and beliefs about cancer, (3) attitudes, behaviours and systems in primary care, (4) delays in diagnosis and treatment, and their causes, and (5) treatment, co-morbidities and other factors. These modules employ a range of methodologies including epidemiological and statistical analyses, surveys and clinical record audit. The first publications have already been used to inform and develop cancer policies in participating countries, and a further series of publications is under way. The module design, governance structure, funding arrangements and management approach to the partnership provide a case study in conducting international comparisons of health systems that are both academically and clinically robust and of immediate relevance to policymakers.